Publication details

Functional cross-talk of integrin b3 and AP-1 in differentiating osteoclasts and dendritic cells.

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Year of publication 2008
Type Article in Proceedings
Conference Book of Abstracts
MU Faculty or unit

Faculty of Medicine

Field Genetics and molecular biology
Keywords osteoclasts; dendritic cells; integrin beta 3; AP-1
Description Osteoclasts (OCL) and dendritic cells (DC) are highly specialized cells that originate from a common hematopoetic progenitor. The osteoclasts are involved in bone resorption; dendritic cells represent a key compound of immune system as antigen presenting cells. Despite distinct functions, similar signaling molecules are involved in control of differentiation of OCL and DC. These regulators include integrin b3, the ECM receptor, and transcription factors c-Jun and c-Fos (AP-1). To investigate the signaling crosstalk between Itgb3 and AP-1 in OCL and DC, we employed murine model of RAW264.7 macrophages. These cells differentiate to OCL or DC upon treatment with RANKL (Receptor activator of NFkB ligand)MCSF or LPS (Lipopolysacharide). Expression of itgb3, c-jun and c-fos as well as differentiation markers were determined at mRNA level by qRT-PCR or western blotting. Expression of itgb3 was induced by both RANKL MCSF and LPS; however, expression of c-fos and c-jun was regulated differently in DC and OCL. Peptides containing Arg-Gly-Asp (RGD) sequence activate Itgb3 pathway specifically and induce expression of c-jun, c-fos and itgb3 in OCL but not in DC upon treatment with LPS. Similarly, inhibition of AP-1 by Jun N terminal kinase inhibitor (JNKi) increases expression of c-fos and itgb3, however it leaves expression of c-jun unaffected upon treatment with MCSF-RANKL or LPS. Moreover, JNKi, but not RGD, completely inhibits the M-CSF/RANKL-induced differentiation of RAW 264.7 cells to OCL and DC. We presume that there is mutual positive regulation between Itgb3- and c-Jun and c-Fos expression in OCL and DC.
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